Estimating long-term effects of disease-modifying drug therapy in multiple sclerosis patients

Richard A. Rudick, G. R. Cutter, M. Baier, B. Weinstock-Guttman, Michele Mass, E. Fisher, D. M. Miller, A. W. Sandrock

Research output: Contribution to journalArticle

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Abstract

Two methods were used to estimate the long-term impact of disease-modifying drug therapy (DMDT) in patients with relapsing multiple sclerosis (MS) who completed a placebo-controlled, randomized clinical trial of interferon beta-1a (IFNβ-1a). The study cohort consisted of patients with ambulatory relapsing MS who had previously participated in a placebo-controlled clinical trial for two years. At its end, patients were managed in an unstructured fashion by their neurologists and re-evaluated at an average of 6.1 years after the end of the trial. Follow-up evaluation was obtained for 93% of the 172 eligible patients. Because study inclusion criteria required that all patients have an Expanded Disability Status Scale (EDSS) score of ≤3.5 at entry, disability progression at follow-up was defined as EDSS ≥6.0. Two methods were used to estimate the expected proportions that reached EDSS ≥6.0 at follow-up. Estimates were compared with observed proportions. Method 1 used progression rates observed during the two-year phase III clinical trial and the percentage of time that patients were on DMDT during the follow-up period. Method 2 used progression rates from a natural history comparison group of relapsing-remitting MS patients. At the eight-year follow-up, 42.0% of the original placebo patients and 29.1% of the original IFNβ-1a patients reached an EDSS ≥6.0, an observed treatment effect of approximately 30%. Using method 1, it was estimated that 36.3% of the original placebo patients and 27.6% of the original IFNβ-1a patients should have reached an EDSS ≥6.0. Use of the natural history control group (method 2) predicted less plausible outcomes. Estimated proportions of patients reaching the endpoint were 63.3% for the original placebo group and 55.8% for the original IFNβ-1a group. Treatment effect sizes of 75-90% would be required to match estimates from method 2 with the observed outcome. The paucity of data on the long-term treatment of patients with MS may be aided by applying these or similar methods to vigorously followed cohorts of patients.

Original languageEnglish (US)
Pages (from-to)626-634
Number of pages9
JournalMultiple Sclerosis
Volume11
Issue number6
DOIs
StatePublished - Dec 2005

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Multiple Sclerosis
Drug Therapy
Placebos
Natural History
Relapsing-Remitting Multiple Sclerosis
Phase III Clinical Trials
Controlled Clinical Trials
Cohort Studies
Therapeutics
Randomized Controlled Trials

Keywords

  • Disease-modifying drug therapy
  • Interferon beta
  • Multiple sclerosis

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Rudick, R. A., Cutter, G. R., Baier, M., Weinstock-Guttman, B., Mass, M., Fisher, E., ... Sandrock, A. W. (2005). Estimating long-term effects of disease-modifying drug therapy in multiple sclerosis patients. Multiple Sclerosis, 11(6), 626-634. https://doi.org/10.1191/1352458505ms1203oa

Estimating long-term effects of disease-modifying drug therapy in multiple sclerosis patients. / Rudick, Richard A.; Cutter, G. R.; Baier, M.; Weinstock-Guttman, B.; Mass, Michele; Fisher, E.; Miller, D. M.; Sandrock, A. W.

In: Multiple Sclerosis, Vol. 11, No. 6, 12.2005, p. 626-634.

Research output: Contribution to journalArticle

Rudick, RA, Cutter, GR, Baier, M, Weinstock-Guttman, B, Mass, M, Fisher, E, Miller, DM & Sandrock, AW 2005, 'Estimating long-term effects of disease-modifying drug therapy in multiple sclerosis patients', Multiple Sclerosis, vol. 11, no. 6, pp. 626-634. https://doi.org/10.1191/1352458505ms1203oa
Rudick, Richard A. ; Cutter, G. R. ; Baier, M. ; Weinstock-Guttman, B. ; Mass, Michele ; Fisher, E. ; Miller, D. M. ; Sandrock, A. W. / Estimating long-term effects of disease-modifying drug therapy in multiple sclerosis patients. In: Multiple Sclerosis. 2005 ; Vol. 11, No. 6. pp. 626-634.
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abstract = "Two methods were used to estimate the long-term impact of disease-modifying drug therapy (DMDT) in patients with relapsing multiple sclerosis (MS) who completed a placebo-controlled, randomized clinical trial of interferon beta-1a (IFNβ-1a). The study cohort consisted of patients with ambulatory relapsing MS who had previously participated in a placebo-controlled clinical trial for two years. At its end, patients were managed in an unstructured fashion by their neurologists and re-evaluated at an average of 6.1 years after the end of the trial. Follow-up evaluation was obtained for 93{\%} of the 172 eligible patients. Because study inclusion criteria required that all patients have an Expanded Disability Status Scale (EDSS) score of ≤3.5 at entry, disability progression at follow-up was defined as EDSS ≥6.0. Two methods were used to estimate the expected proportions that reached EDSS ≥6.0 at follow-up. Estimates were compared with observed proportions. Method 1 used progression rates observed during the two-year phase III clinical trial and the percentage of time that patients were on DMDT during the follow-up period. Method 2 used progression rates from a natural history comparison group of relapsing-remitting MS patients. At the eight-year follow-up, 42.0{\%} of the original placebo patients and 29.1{\%} of the original IFNβ-1a patients reached an EDSS ≥6.0, an observed treatment effect of approximately 30{\%}. Using method 1, it was estimated that 36.3{\%} of the original placebo patients and 27.6{\%} of the original IFNβ-1a patients should have reached an EDSS ≥6.0. Use of the natural history control group (method 2) predicted less plausible outcomes. Estimated proportions of patients reaching the endpoint were 63.3{\%} for the original placebo group and 55.8{\%} for the original IFNβ-1a group. Treatment effect sizes of 75-90{\%} would be required to match estimates from method 2 with the observed outcome. The paucity of data on the long-term treatment of patients with MS may be aided by applying these or similar methods to vigorously followed cohorts of patients.",
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